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  • 1
    ISSN: 1432-0738
    Keywords: Muconaldehyde ; Metabolism ; Mouse liver cytosol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The metabolism of trans,trans-muconaldehyde (MUC), a hematotoxic agent which is a presumed in vivo metabolite of benzene, was studied in mouse liver cytosol. MUC was incubated for 30 min at 37°C with mouse liver cytosol (from CD-1 mice) supplemented with NAD+ and the products were analyzed by reverse phase HPLC. Two products were detected in addition to the previously identified acid-aldehyde 6-oxo-trans,trans-2,4-hexadienoic acid (COOH-M-CHO) and the diacid trans,trans-muconic acid (COOH-M-COOH). Based on the molecular weight (112) obtained by thermo-spray LC-mass spectrometry and the absorbance maximum (269 nm), one of the products was identified as the aldehyde-alcohol 6-hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH). The second product was identified as 6-hydroxy-trans,trans-2,4-hexadienoic acid (COOH-M-OH) by coelution with authentic standard, the fragmentation pattern obtained by electron impact mass spectrometry and the absorbance maximum (258 nm). Time course and concentration dependency studies indicate that COOH-M-OH and COOH-M-COOH are end products of MUC metabolism while CHO-M-OH, and COOH-M-CHO, the initially formed mono-reduction and mono-oxidation products, respectively, are the intermediates leading to these end products. The metabolite COOH-M-OH is formed mainly by oxidation of CHO-M-OH and to a much lesser extent by reduction of CHO-M-COOH, whereas COOH-M-COOH is formed solely by oxidation of COOH-M-CHO. The reduction of MUC to CHO-M-OH is reversible, whereas oxidation to COOH-M-CHO is not. The compound CHO-M-OH is not only oxidized to COOH-M-OH by oxidation of the aldehyde functional group, but is also converted back to MUC by oxidation of the alcohol functional group.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 71 (1997), S. 703-708 
    ISSN: 1432-0738
    Keywords: Key words Distribution ; Muconaldehyde ; Benzene metabolite ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Trans,trans-muconaldehyde (muconaldehyde, MUC), a microsomal hematotoxic ring-opened metabolite of benzene, has been proposed to play a role in benzene hematotoxicity. In the present study, [14C]-muconaldehyde was administered to CD-1 mice and the distribution of [14C]muconaldehyde equivalents was investigated. The study was carried out to evaluate whether [14C]muconaldehyde equivalents could reach the bone marrow. [14C]Muconaldehyde at a dose of 2 mg/kg was administered intraperitoneally (3.4 μCi/mouse) and by intravenous injection (2.7 μCi/mouse). The amount of [14C]muconaldehyde equivalents was measured in the bone marrow, blood, liver, lung, kidney and spleen at 0.25, 0.5, 1, 2, 4, and 24 h after [14C]MUC administration. The results indicate that 0.044% or 0.018% of the total dose administered when given i.v. or i.p., respectively, reached the bone marrow. The elimination of the radioactivity in all organs had at least two phases. The bone marrow, kidney, and lung had a rapid first phase (t 1/2 0.5–1.2 h) and a slower second phase (t 1/2 2.8–15.7 h). In the liver, a slow first phase (t 1/2 3.7 h) was followed by a more rapid second phase (t 1/2 1.5 h). The level of radioactivity in blood and bone marrow was significantly higher when [14C]muconaldehyde was administered intravenously compared with intraperitoneally, demonstrating that the route of administration affects the distribution of [14C]muconaldehyde equivalents.
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  • 3
    ISSN: 1619-1560
    Keywords: baroreceptor ; cardiac rhythm ; blood pressure ; autonomic aerents ; insular cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Representation of cardiovascular function has not been investigated in the human thalamus. In the rat, the insular cortex is the principal forebrain site of cardiovascular representation whose afferents originate from a circumscribed thalamic area (nucleus ventralis posterolateralis-parvicellular portion, VPLpc). We therefore evaluated 4481 thalamic cells for phasic cardiovascular activity using extracellular recording techniques in 60 unanesthetized patients undergoing neurosurgical procedures. We identified 26 cells with phasic activity strongly related to the cardiac cycle in 10 patients. These cells clustered within the ventrocaudal nucleus of the thalamus (the principal sensory nucleus analagous to the ventral posterior thalamic group in the rat and monkey) and were equally distributed between the right and left sides. The majority of these cells (17/26) showed peaks of phasic neuronal activity within 50 ms of the peak systolic pressure; 35% had peripheral cutaneous fields in areas to which cardiac pain is often referred. We suggest that these cells may be involved in the integration of afferent baroreceptor information; may possibly be concerned with the generation and/or processing of central cardiac pain in humans; and that their derangement may possibly contribute to the lethal cardiovascular disturbances which occur in fatal familial insomnia.
    Type of Medium: Electronic Resource
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